Axillary adenopathy after COVID-19 vaccine in patients undergoing breast ultrasound.

After COVID-19 vaccination, a spectrum of axillary lymphadenopathy were observed in patients undergoing routine breast ultrasound. Malignancy remains the most serious differential in cases of unilateral axillary adenopathy. Knowledge of axillary ultrasound findings after COVID-19 vaccination is essential to prevent unnecessary biopsy or change in therapy in oncological patients. From March to May 2021, 10 female patients underwent breast ultrasound in our Department for the evaluation of axillary lumps. All the patients received their first or second dose of COVID-19 vaccine 20-30 days before the exam in the same extremity of the ultrasound evaluation where lymphadenopathy was found. Five patients had a personal history of previous breast cancer, and the radiologist decided to perform a core biopsy (the histology was negative for malignancy). The other five patients with no personal history of cancer underwent ultrasound and returned after a short-term follow-up. Regression of the enlarged lymph nodes was found.

Analysing the attributes of Comprehensive Cancer Centres and Cancer Centres across Europe to identify key hallmarks.

There is a persistent variation in cancer outcomes among and within European countries suggesting (among other causes) inequalities in access to or delivery of high-quality cancer care. European policy (EU Cancer Mission and Europe's Beating Cancer Plan) is currently moving towards a mission-oriented approach addressing these inequalities. In this study, we used the quantitative and qualitative data of the Organisation of European Cancer Institutes' Accreditation and Designation Programme, relating to 40 large European cancer centres, to describe their current compliance with quality standards, to identify the hallmarks common to all centres and to show the distinctive features of Comprehensive Cancer Centres. All Comprehensive Cancer Centres and Cancer Centres accredited by the Organisation of European Cancer Institutes show good compliance with quality standards related to care, multidisciplinarity and patient centredness. However, Comprehensive Cancer Centres on average showed significantly better scores on indicators related to the volume, quality and integration of translational research, such as high-impact publications, clinical trial activity (especially in phase I and phase IIa trials) and filing more patents as early indicators of innovation. However, irrespective of their size, centres show significant variability regarding effective governance when functioning as entities within larger hospitals.

Incidence and characterization of acute pulmonary embolism in patients with SARS-CoV-2 pneumonia: A multicenter Italian experience.

BACKGROUND AND AIMS: Several studies reported a high incidence of pulmonary embolism (PE) among patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but detailed data about clinical characteristics, risk factors of these patients and prognostic role of PE are still lacking. We aim to evaluate the occurrence of pulmonary embolism among patients with SARS-CoV-2 infection, and to describe their risk factors, clinical characteristics, and in-hospital clinical outcomes. METHODS: This is a multicenter Italian study including 333 consecutive SARS-CoV-2 patients admitted to seven hospitals from February 22 to May 15, 2020. All the patients underwent computed tomography pulmonary angiography (CTPA) for PE detection. In particular, CTPA was performed in case of inadequate response to high-flow oxygen therapy (Fi02≥0.4 to maintain Sp02≥92%), elevated D-dimer (>0.5µg/mL), or echocardiographic signs of right ventricular dysfunction. Clinical, laboratory and radiological data were also analyzed. RESULTS: Among 333 patients with laboratory confirmed SARS-CoV-2 pneumonia and undergoing CTPA, PE was detected in 109 (33%) cases. At CTPA, subsegmental, segmental, lobar and central thrombi were detected in 31 (29%), 50 (46%), 20 (18%) and 8 (7%) cases, respectively. In-hospital death occurred in 29 (27%) patients in the PE-group and in 47 (21%) patients in the non-PE group (p = 0.25). Patients in PE-group had a low rate of traditional risk factors and deep vein thrombosis was detected in 29% of patients undergoing compression ultrasonography. In 71% of cases with documented PE, the thrombotic lesions were located in the correspondence of parenchymal consolidation areas. CONCLUSIONS: Despite a low rate of risk factors for venous thromboembolism, PE is present in about 1 out 3 patients with SARS-CoV-2 pneumonia undergoing CTPA for inadequate response to oxygen therapy, elevated D-dimer level, or echocardiographic signs of right ventricular dysfunction. In most of the cases, the thromboses were located distally in the pulmonary tree and were mainly confined within pneumonia areas.

Flat epithelial atypia: conservative management of patients without residual microcalcifications post-vacuum-assisted breast biopsy.

OBJECTIVE: To determine the malignancy rate (defined in this study as stability or absence of malignancy developed on close imaging follow-up post-biopsy) of conservative management in patients with a vacuum-assisted breast biopsy (VAB) diagnosis of flat epithelial atypia (FEA), performed on single group of microcalcifications, completely removed during procedure. METHODS: This is a retrospective, monocentric, observational study, approved by IRB. Inclusion criteria were: VAB performed on a single group of microcalcifications; the absence of residual calcifications post-VAB; diagnosis of isolated FEA as the most advanced proliferative lesion; radiological follow-up at least of 12 months. The personal history of breast cancer or other high-risk lesions was an exclusion criteria. The patients enrolled were conservatively managed, without surgical excision, through close follow-up: the first two mammographies performed with an interval of 6 months after biopsy, followed by annual mammographic and clinical checks. RESULTS: 48 consecutive patients were enrolled in the study, all females, with age range of 39-76 years (mean 53,3 years) and radiological follow-up range of 13-75 months (mean 41.5 months). All the lesions were classified as BI-RADS 4b. The diameter range of the group of calcifications was 3-10 mm (mean 5, 6 mm). In each patient, 7 to 15 samples (mean 11) were obtained. Among all the patients, there was only one case (2%) of new microcalcifications, developed in the same breast, 26 months after and 8 mm from the site of previous VAB, and interpreted as ADH at surgical excision. All the checks of the other patients were negative. CONCLUSION: Even with a limited follow-up, we found a malignancy rate lower than 2%, through a defined population. Further studies with bigger number of patients and extended follow-up are needed to reinforce this hypothesis. Advances in knowledge: Surgical excision may not be necessary in patients with VAB diagnosis of isolated FEA, without residual microcalcifications post-procedure and considered concordant with the mammographic presentation, considering the low rate of malignancy at subsequent follow-ups.

Matricellular proteins and survival in patients with pancreatic cancer: A systematic review.

Extracellular matrix (ECM) plays a fundamental role in tissue architecture and homeostasis and modulates cell functions through a complex interaction between cell surface receptors, hormones, several bioeffector molecules, and structural proteins like collagen. These components are secreted into ECM and all together contribute to regulate several cellular activities including differentiation, apoptosis, proliferation, and migration. The so-called "matricellular" proteins (MPs) have recently emerged as important regulators of ECM functions. The aim of our review is to consider all different types of MPs family assessing the potential relationship between MPs and survival in patients with pancreatic ductal adenocarcinoma (PDAC). A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement issued in 2009 was conducted through Ovid interface, and literature review was performed in May 2017. The search text words were identified by means of controlled vocabulary, such as the National Library of Medicine's MESH (Medical Subject Headings) and Keywords. Collected data showed an important role of MPs in carcinogenesis and in PDAC prognosis even though the underlying mechanisms are still largely unknown and data are not univocal. Therefore, a better understanding of MPs role in regulation of ECM homeostasis and remodeling of specific organ niches may suggest potential novel extracellular targets for the development of efficacious therapeutic strategies.

Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts: Interim Report of a Prospective Comparative Trial.

PURPOSE: Debate on adjunct screening in women with dense breasts has followed legislation requiring that women be informed about their mammographic density and related adjunct imaging. Ultrasound or tomosynthesis can detect breast cancer (BC) in mammography-negative dense breasts, but these modalities have not been directly compared in prospective trials. We conducted a trial of adjunct screening to compare, within the same participants, incremental BC detection by tomosynthesis and ultrasound in mammography-negative dense breasts. PATIENTS AND METHODS: Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts is a prospective multicenter study recruiting asymptomatic women with mammography-negative screens and dense breasts. Eligible women had tomosynthesis and physician-performed ultrasound with independent interpretation of adjunct imaging. Outcome measures included cancer detection rate (CDR), number of false-positive (FP) recalls, and incremental CDR for each modality; these were compared using McNemar's test for paired binary data in a preplanned interim analysis. RESULTS: Among 3,231 mammography-negative screening participants (median age, 51 years; interquartile range, 44 to 78 years) with dense breasts, 24 additional BCs were detected (23 invasive): 13 tomosynthesis-detected BCs (incremental CDR, 4.0 per 1,000 screens; 95% CI, 1.8 to 6.2) versus 23 ultrasound-detected BCs (incremental CDR, 7.1 per 1,000 screens; 95% CI, 4.2 to 10.0), P = .006. Incremental FP recall occurred in 107 participants (3.33%; 95% CI, 2.72% to 3.96%). FP recall (any testing) did not differ between tomosynthesis (FP = 53) and ultrasound (FP = 65), P = .26; FP recall (biopsy) also did not differ between tomosynthesis (FP = 22) and ultrasound (FP = 24), P = .86. CONCLUSION: The Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts' interim analysis shows that ultrasound has better incremental BC detection than tomosynthesis in mammography-negative dense breasts at a similar FP-recall rate. However, future application of adjunct screening should consider that tomosynthesis detected more than 50% of the additional BCs in these women and could potentially be the primary screening modality.

Mammographic density: Comparison of visual assessment with fully automatic calculation on a multivendor dataset.

OBJECTIVES: To compare breast density (BD) assessment provided by an automated BD evaluator (ABDE) with that provided by a panel of experienced breast radiologists, on a multivendor dataset. METHODS: Twenty-one radiologists assessed 613 screening/diagnostic digital mammograms from nine centers and six different vendors, using the BI-RADS a, b, c, and d density classification. The same mammograms were also evaluated by an ABDE providing the ratio between fibroglandular and total breast area on a continuous scale and, automatically, the BI-RADS score. A panel majority report (PMR) was used as reference standard. Agreement (κ) and accuracy (proportion of cases correctly classified) were calculated for binary (BI-RADS a-b versus c-d) and 4-class classification. RESULTS: While the agreement of individual radiologists with the PMR ranged from κ = 0.483 to κ = 0.885, the ABDE correctly classified 563/613 mammograms (92 %). A substantial agreement for binary classification was found for individual reader pairs (κ = 0.620, standard deviation [SD] = 0.140), individual versus PMR (κ = 0.736, SD = 0.117), and individual versus ABDE (κ = 0.674, SD = 0.095). Agreement between ABDE and PMR was almost perfect (κ = 0.831). CONCLUSIONS: The ABDE showed an almost perfect agreement with a 21-radiologist panel in binary BD classification on a multivendor dataset, earning a chance as a reproducible alternative to visual evaluation. KEY POINTS: Individual BD assessment differs from PMR with κ as low as 0.483. An ABDE correctly classified 92 % of mammograms with almost perfect agreement (κ = 0.831). An ABDE can be a valid alternative to subjective BD assessment.

Follow-up of patients with early breast cancer: is it time to rewrite the story?

The guidelines for follow-up in breast cancer survivors support only performance of periodic physical examination and annual mammography. However, medical oncologists and primary care physicians routinely recommend both blood tests and non-mammographic imaging tests in asymptomatic patients, leading to an increased anxiety related to false-positive results and higher medical expenses. Recently, advanced imaging technologies have improved sensitivity/specificity to detect metastatic lesions before symptoms arise. Considering the progress made in the treatment of metastatic disease and the rapid evolution of targeted therapy, that requires customization of the strategy according to molecular characteristics of the disease, patients could derive real benefit to early detection of disease recurrence. This hypothesis must be tested in a prospective clinical trial.

Mammographic density estimation: one-to-one comparison of digital mammography and digital breast tomosynthesis using fully automated software.

OBJECTIVE: To compare breast density on digital mammography and digital breast tomosynthesis using fully automated software. METHODS: Following institutional approval and written informed consent from all participating women, both digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) were obtained. Breast percentage density was calculated with software on DBT and FFDM. RESULTS: Fifty consecutive patients (mean age, 51 years; range, 35-83 years) underwent both FFDM and DBT. Using a method based on the integral curve, breast density showed higher results on FFDM (68.1 ± 12.1 for FFDM and 51.9 ± 6.5 for DBT). FFDM overestimated breast density in 16.2% (P < 0.0001). Using a method based on maximum entropy thresholding, breast density showed higher results on FFDM (68.1 ± 12.1 for FFDM and 51.9 ± 6.5 for DBT). FFDM overestimated breast density in 11.4% (P < 0.0001). There was a good correlation among BI-RADS categories on a four-grade scale and the density evaluated with DBT and FFDM (r = 0.54, P < 0.01 and r = 0.44, P < 0.01). CONCLUSION: Breast density appeared to be significantly underestimated on digital breast tomosynthesis. KEY POINTS: Breast density is considered to be an independent risk factor for cancer Density can be assessed on full-field digital mammography and digital breast tomosynthesis Objective automated estimation of breast density eliminates subjectivity Automated estimation is more accurate than BI-RADS quantitative evaluation Breast density may be significantly underestimated on digital breast tomosynthesis.

A first evaluation of breast radiological density assessment by QUANTRA software as compared to visual classification.

Breast radiological density is a determinant of breast cancer risk and of mammography sensitivity and may be used to personalize screening approach. We first analyzed the reproducibility of visual density assessment by eleven experienced radiologists classifying a set of 418 digital mammograms: reproducibility was satisfactory on a four (BI-RADS D1-2-3-4: weighted kappa = 0.694-0.844) and on a two grade (D1-2 vs D3-4: kappa = 0.620-0.851), but subjects classified as with dense breast would range between 25.1 and 50.5% depending on the classifying reader. Breast density was then assessed by computer using the QUANTRA software which provided systematically lower density percentage values as compared to visual classification. In order to predict visual classification results in discriminating dense and non-dense breast subjects on a two grade scale (D3-4 vs, D1-2) the best fitting cut off value observed for QUANTRA was ≤22.0%, which correctly predicted 88.6% of D1-2, 89.8% of D3-4, and 89.0% of total cases. Computer assessed breast density is absolutely reproducible, and thus to be preferred to visual classification. Thus far few studies have addressed the issue of adjusting computer assessed density to reproduce visual classification, and more similar comparative studies are needed.

One-to-one comparison between digital spot compression view and digital breast tomosynthesis.

OBJECTIVE: To assess if digital breast tomosynthesis (DBT) is at least equal to digital spot compression view (DSCV). METHODS: Following institutional approval and written informed consent, both DBT and DSCV were obtained in women with a screening abnormality. The diagnostic accuracy of DBT and DSCV was evaluated by two radiologists of varying experience (Reader1 and Reader2). RESULTS: 52 consecutive recalled women without calcification (mean age: 51 ± 12 years) underwent DSCV and DBT. Overall sensitivity was equal for both techniques (100% [95% CI, 91-100%] for DBT and 100% [95% CI, 91-100%] for DSCV). Overall specificity was higher for DBT (100% [95%CI, 91-100%]) than for DSCV (94% [95% CI, 91-100%]). Specificity for DSCV was higher for Reader1 (95% [95% CI, 91-100%]). Reader2 had lower values of specificity (92% [95% CI, 90-92%]). On DSCV, three and two false positives were recorded by Reader2 and Reader1, respectively. Overall, the area under the curve (AUC) was greater for DBT (AUC = 1) than for DSCV (AUC = 0.963). The mean difference between the two techniques was not significantly different (P = 0.43). CONCLUSION: In this dataset, diagnostic accuracy of digital breast tomosynthesis is at least equal to that of digital spot compression. KEY POINTS: • Digital spot compression views (DSCVs) are often needed in breast screening programmes. • Digital breast tomosynthesis (DBT) now offers an alternative to DSCV • In recalls without calcification, DBT was at least equally accurate as DSCVs • DBT has a lower mean glandular dose than DSCVs • Thus DBT has the potential to help reduce the recall rate.

The association of human mesenchymal stem cells with BMP-7 improves bone regeneration of critical-size segmental bone defects in athymic rats.

Critical size segmental bone defects are still a major challenge in reconstructive orthopedic surgery. Transplantation of human mesenchymal stem cells (hMSC) has been proposed as an alternative to autogenous bone graft, as MSC can be expanded in vitro and induced to differentiate into bone-regenerating osteoblasts by several bone morphogenetic proteins (BMP). The aim of this study was to investigate whether the association of hMSC and BMP-7, with providing the necessary scaffold to fill the bone loss, improved bone regeneration in a rat model of critical size segmental bone defect, compared to treatment with either hMSC or BMP-7 and the matrix. In addition, we tested whether pre-treatment of hMSC with cyclic ADP-ribose (cADPR), an intracellular Ca2+ mobilizer previously shown to accelerate the in vitro expansion of hMSC (Scarfì S et al, Stem Cells, 2008), affected the osteoinductive capacity of the cells in vivo. X-ray analysis, performed 2, 10 and 16 weeks after transplantation, revealed a significantly higher score in the rats treated with hMSC and BMP-7 compared to controls, receiving either hMSC or BMP-7. Microtomography and histological analysis, performed 16weeks after transplantation, confirmed the improved bone regeneration in the animals treated with the association of hMSC and BMP-7 compared to controls. Pre-treatment with cADPR to stimulate hMSC proliferation in vitro did not affect the bone regenerating capacity of the cells in vivo. These results indicate that the association of in vitro expanded hMSC with BMP-7 provide a better osteoinductive graft compared to either hMSC or BMP-7 alone. Moreover, cADPR may be used to stimulate hMSC proliferation in vitro in order to reduce the time required to obtain a transplantable number of cells, with no adverse effect on the bone regenerating capacity of hMSC.

Reconstruction of extensive long bone defects in sheep using resorbable bioceramics based on silicon stabilized tricalcium phosphate.

In this study we evaluated the performance of Skelite, a resorbable bioceramic based on silicon stabilized tricalcium phosphate (Si-TCP), in promoting the repair of a large-sized, experimentally induced defect in a weight-bearing long bone sheep model. Eighteen 2-year-old ewes were used in this study. Animals were sacrificed at 3, 6, and 12 months. One animal entered a very prolonged followup and was sacrificed 2 years after surgery. Bone formation and scaffold resorption were evaluated by sequential x-ray studies, CT scans, histology, immunohistology, microradiography, and quantitative analysis of x-ray studies (optical density) and microradiographs (percentage of bone and scaffold area). Our data show an excellent implant integration and significant bone regeneration within the bone substitute over the course of the experiment. Progressive osteoclastic resorption of the biomaterial was also evident. At 1 year from surgery, the remaining scaffold was approximately 10-20% of the scaffold initially implanted, while after 2 years it was essentially completely resorbed. At the end of the observation period, the segmental defect was filled with newly formed, highly mineralized, lamellar bone.

Induction chemotherapy with carboplatin-paclitaxel followed by standard radiotherapy with concurrent daily low-dose cisplatin plus weekly paclitaxel for inoperable non-small-cell lung cancer.

Both induction chemotherapy and concurrent platinating agents have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase II study investigated activity and feasibility of a novel chemoradiation regimen, including platinum and paclitaxel, both as induction chemotherapy and concurrently with thoracic radiotherapy. Previously untreated patients with histologically/cytologically proven unresectable stage I-III NSCLC were eligible. Induction chemotherapy consisted of 2 courses of 200 mg/m2 paclitaxel and carboplatin at AUC of 6 mg/mL/min every 3 weeks. From day 43, continuous thoracic irradiation (60 Gy in 30 fractions radiotherapy for 6 weeks) was given concurrently with daily cisplatin at a dose of 5 mg/m2 intravenously and weekly paclitaxel at a dose of 45 mg/m2 for 6 weeks. Fifteen patients were accrued in the first stage of the trial. According to the previous statistical considerations, accrual at the second stage of the study was halted as a result of the achievement an insufficient number of successes. Major toxicity of combined chemoradiation was grade III-IV esophagitis requiring hospitalization for artificial nutrition, which occurred in 58% of patients. Other toxicities included grade II-IV fatigue in 75% of patients and grade I-IV neuromuscular toxicity in 67%. Only 7 patients completed the treatment program as scheduled. Eight patients (53.3%; 95% confidence interval, 26.5-78.7%) had a major response (5 partial response, 3 complete response), 2 patients had disease progression, and 1 was stable at the end of treatment. Four patients died early. With a median follow up of 38 months, the median survival was 12 months. A combined chemoradiation program, including platinum and paclitaxel, appears difficult to deliver at full dose as a result of toxicity, mainly esophagitis. More active and less toxic combined modality treatments need to be developed for inoperable NSCLC.

Somatostatin receptor scintigraphy for bronchial carcinoid follow-up.

PURPOSE: Somatostatin receptor scintigraphy (SRS) has been used to diagnose bronchial carcinoids (BC) and is a valuable tool for accurate staging of BC. The aim of this study was to evaluate the role of SRS in restaging BC and following patients after treatment. METHODS: Thirty-one patients (18 male, 13 female) with confirmed BC who were referred during the last 7 years were included. Patients were examined via chest radiograph (12 studies), chest or abdominal computed tomography (CT; 28 scans), chest magnetic resonance imaging (2 scans), and liver ultrasound (5 scans). RESULTS: Overall, in 22 patients (71%), SRS confirmed the data obtained by other diagnostic procedures (16 negative and 6 positive findings). In 6 patients, SRS showed focal lesions not previously demonstrated. In 2 patients, SRS resolved uncertain findings of CT. In 1 patient, SRS showed fewer lesions compared with CT. In 8 of 31 patients, important diagnostic information obtained by SRS was not revealed by any other imaging procedure. CONCLUSION: Our results indicate that SRS is a reliable, noninvasive method that could be considered the principal follow-up procedure in patients with BC.